HIGH-CAPACITY SCREENING OF POOLED COMPOUNDS - IDENTIFICATION OF THE ACTIVE COMPOUND WITHOUT RE-ASSAY OF POOL MEMBERS

A matrix-based compound pooling and deconvolution method has been deve loped that significantly increased the efficiency of a high-capacity s creening program. This method is based on screening pools of 10 compou nds. The matrix used to assemble the pools resulted in each compound b eing assayed twice-each time with a completely different set of pooled compounds. The active compound in an active pool was accurately predi cted by determining which compound was present in an active pool both times that a pool containing that compound was tested. This has elimin ated the need to re-assay each individual member of active pools. This approach has been tested with a set of 6,680 compounds in three diffe rent assays: inhibition of Factor Xa, inhibition of gastrin-releasing peptide receptor binding, and inhibition of nitric oxide synthase (iso form II). Thus significant time is saved not only by pooling the compo unds for the initial assay but also by avoiding the need to re-assay a ll compounds in active pools. Moreover, no false negatives occurred in these assays-an important consideration from a drug discovery perspec tive. (C) 1996 Wiley-Liss, Inc.